Yaguang Fan

China national lung cancer screening guideline with low‐dose computed tomography (2015 version)

Lung cancer is the leading cause of cancer‐related death in China. Results from a randomized controlled trial using annual low‐dose computed tomography (LDCT) in specific high‐risk groups demonstrated a 20% reduction in lung cancer mortality.

Association Between Sputum Atypia and Lung Cancer Risk in an Occupational Cohort in Yunnan, China

BACKGROUND Individuals with cytologic atypia in sputum may be at high risk for the development of lung cancer. METHODS A prospective cohort study was conducted among occupational tin miners in Yunnan, China, based on an annual lung cancer screening program. Sputum samples were collected prospectively at baseline and the following seven annual screenings. The associations between risk factors and sputum cytology were analyzed by univariate and multivariate logistic regression. A proportional hazard model was used to analyze the association between the baseline sputum results and the incidence of lung cancer. The effect of consecutive sputum cytology on the increase of lung cancer risk was analyzed by logistic regression. RESULTS Sputum cytologic atypia was associated with age, smoking, occupational radon and arsenic exposure, and asthma. Sputum cytologic atypia was an independent risk factor for lung cancer with an adjusted hazard ratio (HR) of 3.82 (95% confidence interval [CI], 2.82 to 5.18) in comparing normal to moderate or worse atypia. Compared to the lung cancer risk associated with normal sputum, the risk was significantly higher according to the degree of atypia for squamous carcinomas, small cell lung cancer and central lung cancer, with adjusted HRs of 5.70 (95% CI, 3.78 to 8.59), 3.32 (95% CI, 1.31 to 8.45), and 4.93 (95% CI, 3.51 to 6.92), respectively. CONCLUSIONS Sputum atypia is associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may play an important role in the early detection of lung cancer or in the selection of the optimal target population for more intensive lung cancer screening among this occupational cohort or similar population.

Prior lung disease and lung cancer risk in an occupational-based cohort in Yunnan, China

We used the data from a prospective cohort study among tin miners in Yunnan, China to investigate whether prior lung disease is a risk factor for lung cancer. Information on prior lung disease was obtained from baseline questionnaires. The Cox proportional hazards model was used to examine the relationship between prior lung disease and lung cancer risk. From 1992 to 2001, a total of 502 lung cancer cases were confirmed among 9295 cohort participants. Prior chronic bronchitis was associated with an increase in lung cancer risk with an adjusted HR of 1.50 (95% CI: 1.24-1.81). There was an increased risk of developing squamous cell carcinoma in the setting of prior chronic bronchitis and small cell carcinoma in association with asthma with an adjusted HRs of 1.57 (95% CI: 1.19-2.09) and 2.56 (95% CI: 1.38-4.75), respectively. This prospective study provides further evidence that prior chronic bronchitis correlates with increased lung cancer risk, especially for squamous cell carcinoma. Asthma is associated with increased risk of small cell lung carcinoma.

Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer

ABSTRACT Although metastasis remains the overwhelming cause of death for patients with non-small cell lung cancer (NSCLC), the underlying mechanisms of metastasis remain unknown. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor cell invasion and metastasis. Expression of miR-9, miR-10b, miR-145, and miR-155, 4 miRNAs previously shown to play roles in metastasis in other tumor types, was compared in lymph node (LN)-positive NSCLC versus LN-negative NSCLC. Expression of miR-145 was significantly lower in LN-positive NSCLC (P < 0.05), while expression of miR-10b was significantly higher (P < 0.05). Expression of both miR-145 and miR-10b was correlated with lymph node metastasis in NSCLC (both Ps < 0.001). In addition, miR-10b facilitated the migration and invasion of lung cancer cell line A549, while miR-145 suppressed the migration and invasion capacity of A549 in vitro. These results suggest that miR-10b and miR-145 may act as an oncogene or tumor suppressor gene, respectively, in NSCLC metastasis.

Esophageal cancer incidence and mortality in China, 2010.

The National Central Cancer Registry of China (NCCR) is responsible for cancer surveillance. Local cancer registries in each province submit data for annual publication.. The incidence and mortality of esophageal cancer in China in 2010 by age, gender, and area is reported in this article.

Demonstration program of population‐based lung cancer screening in China: Rationale and study design

Lung cancer is the leading cause of cancer‐related death and has become an enormous economic burden in China. Low‐dose spiral computed tomography (LDCT) screening could reduce lung cancer mortality. The feasibility of conducting a population‐based lung cancer screening with LDCT in China is uncertain.

Lung cancer incidence and mortality in China, 2011: Lung cancer statistics in China, 2011

The National Central Cancer Registry of China (NCCR) is responsible for cancer surveillance. Local cancer registries in each province submit data for annual publication. The incidence and mortality of lung cancer in China in 2010 by age, gender, and area is reported in this article.

MiR-146b-5p functions as a suppressor miRNA and prognosis predictor in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. However, science has not yet been able to substantially improve the prognosis of lung cancer patients. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor development and metastasis. Expression of six miRNAs previously shown to play roles in tumor development (miR-146b-5p, miR-128b, miR-21, miR-221, miR-34a, and Let-7a) in other tumor types was examined using real-time RT-PCR in 78 specimens of NSCLC. The results revealed that patients with low expression of miR-146b-5p had significant shorter median and mean survival time than those with high miR-146b-5p expression (33.00 and 30.44 months versus 42.0 and 36.90 months, respectively; log-rank test P=0.048), thus low miR-146b-5p expression level was associated with poor prognosis in NSCLC patients. Univariate Cox hazard regression analysis demonstrated that miR-146b-5p expression levels tended to be a significant prognostic indicator of NSCLC (adjusted hazard ratio=0.482, 95% CI: 1.409- 29.593, P=0.016). Multivariate Cox proportional hazard regression analysis showed that miR-146b-5p expression levels were an independent prognostic factor for NSCLC patients (hazard ratio=0.259, 95% CI: 0.083-0.809, P=0.020). Furthermore, the effects of miR-146b-5p and miR-146b-3p on NSCLC cell growth and invasion in vitro were investigated. Our findings demonstrate that ectopic expression of miR-146b-5p suppressed cell proliferation, clonogenicity, migration/ invasion and also induced G1 arrest in vitro, but did not induce cell apoptosis; whereas enforced expression of miR-146b-3p did not have a significant effect on cell growth and metastasis. Further experiments indicated that miR-146b-5p could reduce mRNA levels of MMP16 and TRAF6 in vitro and was negatively related to the expression of TRAF6 in human NSCLC tissues. In a mouse model, Ago-miR-146b-5p could significantly inhibit the growth of lung cancer xenografts in nude mice. In conclusion, our findings demonstrate that miR-146b-5p functions as a suppressor miRNA and prognosis predictor in NSCLC.

Attributable causes of lung cancer incidence and mortality in China

The aims of our study were to estimate the contribution of known lung cancer risk factors, and provide evidence to support the National Cancer Prevention and Control Program in China. We calculated the proportion of lung cancer attributable to specific risk factors. Data on exposure prevalence were from meta‐analyses and large‐scale national surveys of representative samples of the Chinese population. Data on relative risks were from meta‐analyses and large‐scale prospective studies. Lung cancer mortality and incidence were taken from the Third National Death Survey and from cancer registries in China. We estimated that in China 285 304 lung cancer deaths and 327 465 cases were attributable to smoking, involuntary smoking (women only), occupational exposure, indoor radon, and low fruit intake in 2005. The proportion of lung cancer deaths attributable to smoking, involuntary smoking among non‐smoking women, occupational exposure, indoor radon and low fruit intake was 56.9%, 11.1%, 9.5%, 0.2% and 12.4%, respectively. About 41% of lung cancer mortality and incidence in women was caused by risk factors in our study. However, over half of lung cancer deaths and cases among women were not attributable to known risk factors. It is necessary to conduct large‐scale studies to identify additional risk factors of lung cancer in non‐smoking women.

Thyroid transcription factor-1 expression is significantly associated with mutations in exon 21 of the epidermal growth factor receptor gene in Chinese patients with lung adenocarcinoma.

Objective The aim of this retrospective study was to investigate the relationship between thyroid transcription factor-1 (TTF-1) expression and epidermal growth factor receptor (EGFR) gene mutations in lung adenocarcinomas of Chinese patients. Methods There were 200 lung adenocarcinoma patients who were enrolled in this study. Tumor specimens of these patients were investigated for TTF-1 expression and mutations in EGFR using immunohistochemistry and a liquid chip platform for DNA analysis of slides with sections of formalin-fixed, paraffin-embedded specimens. Results The rates of TTF-1 expression and EGFR mutations were 81.5% and 45.5%, respectively, in the lung adenocarcinoma specimens of the recruited patients. Among female nonsmokers (n=72), 93.1% of specimens were positive for TTF-1 expression, and 63.9% had EGFR mutations. Of 89 patients with EGFR mutations, 83 (50.9%) specimens were simultaneously positive for TTF-1 expression. Kaplan–Meier analysis of all patient specimens found that postoperative survival time was not significantly associated with TTF-1 expression and the presence of EGFR mutations. However, patients with disease stages III–IV whose tumors were positive for TTF-1 expression and EGFR mutations had better postoperative survival than similar patients whose tumors were negative for TTF-1 expression and EGFR mutations. Conclusion Our study showed a significant association between TTF-1 positivity and the presence of EGFR mutations (exon 21) in the Chinese lung adenocarcinoma patients. We further identify that patients with disease stages III–IV who were positive for TTF-1 expression and EGFR mutations had a better postoperative survival than those patients who were negative for TTF-1 expression and EGFR mutations. Therefore, TTF-1 might be a potential prognostic biomarker for stages III–IV lung adenocarcinoma patients. In clinical practice, TTF-1 expression may be a marker for planning therapy for certain patients with lung adenocarcinoma, especially for selection of EGFR tyrosine kinase inhibitors.